CA2220060A1 - A method for increasing the electrotransport flux of polypeptides - Google Patents

A method for increasing the electrotransport flux of polypeptides Download PDF

Info

Publication number: CA2220060A1
Authority: CA; Canada
Prior art keywords: polypeptide; analog; pth; parent; amino acid
Prior art date: 1995-06-06
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002220060A

Other languages

English (en)

French (fr)

Inventor

Leslie A. Holladay

Kevin R. Oldenburg

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Alza Corp

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-06-06

Filing date

1996-06-06

Publication date

1996-12-12

1996-06-06 Application filed by Individual filed Critical Individual

1996-12-12 Publication of CA2220060A1 publication Critical patent/CA2220060A1/en

Status Abandoned legal-status Critical Current

Links

108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 145
102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 121
229920001184 polypeptide Polymers 0.000 title claims abstract description 113
238000000034 method Methods 0.000 title claims abstract description 48
230000004907 flux Effects 0.000 title abstract description 52
230000001965 increasing effect Effects 0.000 title description 7
239000003795 chemical substances by application Substances 0.000 claims abstract description 32
125000000539 amino acid group Chemical group 0.000 claims abstract description 31
239000000203 mixture Substances 0.000 claims abstract description 9
108090000445 Parathyroid hormone Proteins 0.000 claims description 80
102000003982 Parathyroid hormone Human genes 0.000 claims description 79
239000000199 parathyroid hormone Substances 0.000 claims description 76
229960001319 parathyroid hormone Drugs 0.000 claims description 76
108010025036 hirulog-B2 Proteins 0.000 claims description 36
125000003275 alpha amino acid group Chemical group 0.000 claims description 14
OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical group C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 claims description 14
108010055460 bivalirudin Proteins 0.000 claims description 12
229960001500 bivalirudin Drugs 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 6
230000004071 biological effect Effects 0.000 claims description 2
230000000368 destabilizing effect Effects 0.000 abstract description 2
239000003814 drug Substances 0.000 description 56
229940079593 drug Drugs 0.000 description 53
235000001014 amino acid Nutrition 0.000 description 35
108090000623 proteins and genes Proteins 0.000 description 32
229940024606 amino acid Drugs 0.000 description 31
235000018102 proteins Nutrition 0.000 description 29
210000003491 skin Anatomy 0.000 description 29
150000001413 amino acids Chemical class 0.000 description 28
102000004169 proteins and genes Human genes 0.000 description 28
-1 carboxyphenyl Chemical group 0.000 description 27
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 26
210000004027 cell Anatomy 0.000 description 23
239000000499 gel Substances 0.000 description 17
239000000243 solution Substances 0.000 description 17
241000282320 Panthera leo Species 0.000 description 16
239000013612 plasmid Substances 0.000 description 16
238000002347 injection Methods 0.000 description 12
239000007924 injection Substances 0.000 description 12
230000001070 adhesive effect Effects 0.000 description 10
238000004364 calculation method Methods 0.000 description 10
238000012377 drug delivery Methods 0.000 description 10
238000000338 in vitro Methods 0.000 description 10
239000000853 adhesive Substances 0.000 description 9
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 9
238000001990 intravenous administration Methods 0.000 description 9
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 8
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
239000000872 buffer Substances 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000000017 hydrogel Substances 0.000 description 8
239000011159 matrix material Substances 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 7
230000008030 elimination Effects 0.000 description 7
238000003379 elimination reaction Methods 0.000 description 7
241000894007 species Species 0.000 description 7
238000007920 subcutaneous administration Methods 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
108020004414 DNA Proteins 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
229910052774 Proactinium Inorganic materials 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
230000001939 inductive effect Effects 0.000 description 6
230000000977 initiatory effect Effects 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
229920000642 polymer Polymers 0.000 description 6
238000004448 titration Methods 0.000 description 6
108020004705 Codon Proteins 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
102000004877 Insulin Human genes 0.000 description 5
108090001061 Insulin Proteins 0.000 description 5
102000035195 Peptidases Human genes 0.000 description 5
108091005804 Peptidases Proteins 0.000 description 5
241000282898 Sus scrofa Species 0.000 description 5
239000007983 Tris buffer Substances 0.000 description 5
239000002253 acid Substances 0.000 description 5
230000007423 decrease Effects 0.000 description 5
WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical class C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 5
230000008569 process Effects 0.000 description 5
239000000523 sample Substances 0.000 description 5
210000000434 stratum corneum Anatomy 0.000 description 5
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
239000013598 vector Substances 0.000 description 5
YFONKFDEZLYQDH-OPQQBVKSSA-N N-[(1R,2S)-2,6-dimethyindan-1-yl]-6-[(1R)-1-fluoroethyl]-1,3,5-triazine-2,4-diamine Chemical compound C[C@@H](F)C1=NC(N)=NC(N[C@H]2C3=CC(C)=CC=C3C[C@@H]2C)=N1 YFONKFDEZLYQDH-OPQQBVKSSA-N 0.000 description 4
238000009825 accumulation Methods 0.000 description 4
238000007792 addition Methods 0.000 description 4
238000003556 assay Methods 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 4
210000003000 inclusion body Anatomy 0.000 description 4
229940125396 insulin Drugs 0.000 description 4
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
230000007017 scission Effects 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
QJPWUUJVYOJNMH-VKHMYHEASA-N L-homoserine lactone Chemical compound N[C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-N 0.000 description 3
108091034117 Oligonucleotide Proteins 0.000 description 3
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
108020004511 Recombinant DNA Proteins 0.000 description 3
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
241000282887 Suidae Species 0.000 description 3
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
239000006184 cosolvent Substances 0.000 description 3
238000005370 electroosmosis Methods 0.000 description 3
210000002615 epidermis Anatomy 0.000 description 3
239000012634 fragment Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
229920002521 macromolecule Polymers 0.000 description 3
239000002773 nucleotide Substances 0.000 description 3
125000003729 nucleotide group Chemical group 0.000 description 3
230000000849 parathyroid Effects 0.000 description 3
239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
229940002612 prodrug Drugs 0.000 description 3
239000000651 prodrug Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 3
238000000746 purification Methods 0.000 description 3
150000003839 salts Chemical group 0.000 description 3
238000005070 sampling Methods 0.000 description 3
238000012216 screening Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
KRKRAOXTGDJWNI-UHFFFAOYSA-N 4-Methylglutamic acid Chemical compound OC(=O)C(C)CC(N)C(O)=O KRKRAOXTGDJWNI-UHFFFAOYSA-N 0.000 description 2
241001136792 Alle Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
108010065372 Dynorphins Proteins 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
108010007267 Hirudins Proteins 0.000 description 2
102000007625 Hirudins Human genes 0.000 description 2
MBZXSJWDBIIBLL-GDVGLLTNSA-N Homoisoleucine Chemical compound CCC(C)C[C@H](N)C(O)=O MBZXSJWDBIIBLL-GDVGLLTNSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
108010076504 Protein Sorting Signals Proteins 0.000 description 2
IDIDJDIHTAOVLG-VKHMYHEASA-N S-methylcysteine Chemical compound CSC[C@H](N)C(O)=O IDIDJDIHTAOVLG-VKHMYHEASA-N 0.000 description 2
244000180577 Sambucus australis Species 0.000 description 2
235000018734 Sambucus australis Nutrition 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
239000008351 acetate buffer Substances 0.000 description 2
230000004075 alteration Effects 0.000 description 2
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
229960000723 ampicillin Drugs 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
239000012148 binding buffer Substances 0.000 description 2
230000008033 biological extinction Effects 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
238000002983 circular dichroism Methods 0.000 description 2
238000010367 cloning Methods 0.000 description 2
239000013599 cloning vector Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000012217 deletion Methods 0.000 description 2
230000037430 deletion Effects 0.000 description 2
OGGXGZAMXPVRFZ-UHFFFAOYSA-M dimethylarsinate Chemical compound C[As](C)([O-])=O OGGXGZAMXPVRFZ-UHFFFAOYSA-M 0.000 description 2
230000002708 enhancing effect Effects 0.000 description 2
230000001747 exhibiting effect Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000013604 expression vector Substances 0.000 description 2
239000006260 foam Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
229940006607 hirudin Drugs 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
239000006193 liquid solution Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000003607 modifier Substances 0.000 description 2
239000000813 peptide hormone Substances 0.000 description 2
238000010647 peptide synthesis reaction Methods 0.000 description 2
229920003023 plastic Polymers 0.000 description 2
239000004033 plastic Substances 0.000 description 2
229920000573 polyethylene Polymers 0.000 description 2
229920002704 polyhistidine Polymers 0.000 description 2
239000000047 product Substances 0.000 description 2
238000010188 recombinant method Methods 0.000 description 2
229920005989 resin Polymers 0.000 description 2
239000011347 resin Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
238000010532 solid phase synthesis reaction Methods 0.000 description 2
229920001059 synthetic polymer Polymers 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
HYGGRRPFVXHQQW-YFKPBYRVSA-N (2r)-2-amino-3-prop-1-enylsulfanylpropanoic acid Chemical compound CC=CSC[C@H](N)C(O)=O HYGGRRPFVXHQQW-YFKPBYRVSA-N 0.000 description 1
BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
CGRCVIZBNRUWLY-HNNXBMFYSA-N (2s)-2-[(4-methylphenyl)sulfonylamino]-3-phenylpropanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CGRCVIZBNRUWLY-HNNXBMFYSA-N 0.000 description 1
SULKGYKWHKPPKO-RAJPIYRYSA-N (4s)-4-[[(2r)-2-[[(2s,3r)-2-[[(2s)-4-amino-4-oxo-2-[[(2s)-pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-hydroxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-5-[[(2s,3s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s,3r)-1-[[2-[[(1r)-1-carboxy Chemical compound N([C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CS)C(O)=O)[C@@H](C)O)C(=O)[C@@H]1CCCN1 SULKGYKWHKPPKO-RAJPIYRYSA-N 0.000 description 1
UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
HFDKKNHCYWNNNQ-YOGANYHLSA-N 75976-10-2 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C1=CC=C(O)C=C1 HFDKKNHCYWNNNQ-YOGANYHLSA-N 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
102100027211 Albumin Human genes 0.000 description 1
101100002068 Bacillus subtilis (strain 168) araR gene Proteins 0.000 description 1
101100277726 Bacillus subtilis (strain 168) sul gene Proteins 0.000 description 1
101001135732 Bos taurus Parathyroid hormone Proteins 0.000 description 1
101100275473 Caenorhabditis elegans ctc-3 gene Proteins 0.000 description 1
102400000113 Calcitonin Human genes 0.000 description 1
108060001064 Calcitonin Proteins 0.000 description 1
241000700198 Cavia Species 0.000 description 1
101800001982 Cholecystokinin Proteins 0.000 description 1
102100025841 Cholecystokinin Human genes 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
102100021752 Corticoliberin Human genes 0.000 description 1
101710113174 Corticoliberin Proteins 0.000 description 1
101800000414 Corticotropin Proteins 0.000 description 1
244000303965 Cyamopsis psoralioides Species 0.000 description 1
101710095468 Cyclase Proteins 0.000 description 1
150000008574 D-amino acids Chemical group 0.000 description 1
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 1
229930182832 D-phenylalanine Natural products 0.000 description 1
102000016911 Deoxyribonucleases Human genes 0.000 description 1
108010053770 Deoxyribonucleases Proteins 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
101100289061 Drosophila melanogaster lili gene Proteins 0.000 description 1
108010049140 Endorphins Proteins 0.000 description 1
102000009025 Endorphins Human genes 0.000 description 1
102000002045 Endothelin Human genes 0.000 description 1
108050009340 Endothelin Proteins 0.000 description 1
241001302160 Escherichia coli str. K-12 substr. DH10B Species 0.000 description 1
241001524679 Escherichia virus M13 Species 0.000 description 1
102000009123 Fibrin Human genes 0.000 description 1
108010073385 Fibrin Proteins 0.000 description 1
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
108010067306 Fibronectins Proteins 0.000 description 1
102000016359 Fibronectins Human genes 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
102400001370 Galanin Human genes 0.000 description 1
101800002068 Galanin Proteins 0.000 description 1
102400000921 Gastrin Human genes 0.000 description 1
108010052343 Gastrins Proteins 0.000 description 1
206010070840 Gastrointestinal tract irritation Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102400000321 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
102400001367 Guanylin Human genes 0.000 description 1
101800004305 Guanylin Proteins 0.000 description 1
101001135770 Homo sapiens Parathyroid hormone Proteins 0.000 description 1
101001135995 Homo sapiens Probable peptidyl-tRNA hydrolase Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
108091092195 Intron Proteins 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
FSBIGDSBMBYOPN-VKHMYHEASA-N L-canavanine Chemical compound OC(=O)[C@@H](N)CCONC(N)=N FSBIGDSBMBYOPN-VKHMYHEASA-N 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
WZNJWVWKTVETCG-YFKPBYRVSA-N L-mimosine Chemical compound OC(=O)[C@@H](N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-YFKPBYRVSA-N 0.000 description 1
SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
XNSAINXGIQZQOO-UHFFFAOYSA-N L-pyroglutamyl-L-histidyl-L-proline amide Natural products NC(=O)C1CCCN1C(=O)C(NC(=O)C1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-UHFFFAOYSA-N 0.000 description 1
108010054278 Lac Repressors Proteins 0.000 description 1
239000006137 Luria-Bertani broth Substances 0.000 description 1
108060003100 Magainin Proteins 0.000 description 1
101100301239 Myxococcus xanthus recA1 gene Proteins 0.000 description 1
102400001103 Neurotensin Human genes 0.000 description 1
101800001814 Neurotensin Proteins 0.000 description 1
108091028043 Nucleic acid sequence Proteins 0.000 description 1
FSBIGDSBMBYOPN-UHFFFAOYSA-N O-guanidino-DL-homoserine Natural products OC(=O)C(N)CCON=C(N)N FSBIGDSBMBYOPN-UHFFFAOYSA-N 0.000 description 1
108010038807 Oligopeptides Proteins 0.000 description 1
102000015636 Oligopeptides Human genes 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
102400000203 Pancreastatin Human genes 0.000 description 1
101800005322 Pancreastatin Proteins 0.000 description 1
102000018886 Pancreatic Polypeptide Human genes 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
241001674048 Phthiraptera Species 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
102100027467 Pro-opiomelanocortin Human genes 0.000 description 1
102100024622 Proenkephalin-B Human genes 0.000 description 1
239000004365 Protease Substances 0.000 description 1
101150107341 RERE gene Proteins 0.000 description 1
IDIDJDIHTAOVLG-UHFFFAOYSA-N S-methyl-L-cysteine Natural products CSCC(N)C(O)=O IDIDJDIHTAOVLG-UHFFFAOYSA-N 0.000 description 1
108010086019 Secretin Proteins 0.000 description 1
102100037505 Secretin Human genes 0.000 description 1
229910021607 Silver chloride Inorganic materials 0.000 description 1
206010040914 Skin reaction Diseases 0.000 description 1
102100022831 Somatoliberin Human genes 0.000 description 1
101710142969 Somatoliberin Proteins 0.000 description 1
108091081024 Start codon Proteins 0.000 description 1
240000001058 Sterculia urens Species 0.000 description 1
235000015125 Sterculia urens Nutrition 0.000 description 1
101000983124 Sus scrofa Pancreatic prohormone precursor Proteins 0.000 description 1
108010046075 Thymosin Proteins 0.000 description 1
102000007501 Thymosin Human genes 0.000 description 1
239000000627 Thyrotropin-Releasing Hormone Substances 0.000 description 1
102400000336 Thyrotropin-releasing hormone Human genes 0.000 description 1
101800004623 Thyrotropin-releasing hormone Proteins 0.000 description 1
229910052770 Uranium Inorganic materials 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
238000010171 animal model Methods 0.000 description 1
238000005349 anion exchange Methods 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
229940127219 anticoagulant drug Drugs 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
101150044616 araC gene Proteins 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
239000003899 bactericide agent Substances 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
SRBFZHDQGSBBOR-KLVWXMOXSA-N beta-L-arabinopyranose Chemical compound O[C@H]1CO[C@H](O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-KLVWXMOXSA-N 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000000975 bioactive effect Effects 0.000 description 1
229920001222 biopolymer Polymers 0.000 description 1
101150049515 bla gene Proteins 0.000 description 1
239000002981 blocking agent Substances 0.000 description 1
DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
229960004015 calcitonin Drugs 0.000 description 1
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
229940041514 candida albicans extract Drugs 0.000 description 1
239000002775 capsule Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000005341 cation exchange Methods 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
229920003086 cellulose ether Polymers 0.000 description 1
230000008859 change Effects 0.000 description 1
230000009920 chelation Effects 0.000 description 1
AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
229940107137 cholecystokinin Drugs 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000010276 construction Methods 0.000 description 1
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
229960000258 corticotropin Drugs 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
ORQXBVXKBGUSBA-UHFFFAOYSA-N cyclohexyl D-alanine Natural products OC(=O)C(N)CC1CCCCC1 ORQXBVXKBGUSBA-UHFFFAOYSA-N 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
PLMFYJJFUUUCRZ-UHFFFAOYSA-M decyltrimethylammonium bromide Chemical compound [Br-].CCCCCCCCCC[N+](C)(C)C PLMFYJJFUUUCRZ-UHFFFAOYSA-M 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
101150106284 deoR gene Proteins 0.000 description 1
YFHLIDBAPTWLGU-CTKMSOPVSA-N dermaseptin Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)N)[C@@H](C)O)[C@@H](C)O)C1=CN=CN1 YFHLIDBAPTWLGU-CTKMSOPVSA-N 0.000 description 1
229940049701 dermaseptin Drugs 0.000 description 1
108090000454 dermaseptin Proteins 0.000 description 1
239000003599 detergent Substances 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000000539 dimer Substances 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
JMNJYGMAUMANNW-FIXZTSJVSA-N dynorphin a Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 JMNJYGMAUMANNW-FIXZTSJVSA-N 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
239000013536 elastomeric material Substances 0.000 description 1
230000005518 electrochemistry Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000012149 elution buffer Substances 0.000 description 1
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
238000001976 enzyme digestion Methods 0.000 description 1
239000005038 ethylene vinyl acetate Substances 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
229950003499 fibrin Drugs 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000012737 fresh medium Substances 0.000 description 1
230000004927 fusion Effects 0.000 description 1
101150045500 galK gene Proteins 0.000 description 1
101150041954 galU gene Proteins 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
101150096208 gtaB gene Proteins 0.000 description 1
230000023597 hemostasis Effects 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
230000010224 hepatic metabolism Effects 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
230000003284 homeostatic effect Effects 0.000 description 1
QJPWUUJVYOJNMH-UHFFFAOYSA-N homoserine lactone Chemical compound NC1CCOC1=O QJPWUUJVYOJNMH-UHFFFAOYSA-N 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
239000003668 hormone analog Substances 0.000 description 1
102000058004 human PTH Human genes 0.000 description 1
238000009396 hybridization Methods 0.000 description 1
235000011167 hydrochloric acid Nutrition 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000002955 immunomodulating agent Substances 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000004026 insulin derivative Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
229920000831 ionic polymer Polymers 0.000 description 1
239000002563 ionic surfactant Substances 0.000 description 1
230000007794 irritation Effects 0.000 description 1
238000002955 isolation Methods 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
101150023497 mcrA gene Proteins 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229950002289 mimosine Drugs 0.000 description 1
244000309715 mini pig Species 0.000 description 1
SLZIZIJTGAYEKK-CIJSCKBQSA-N molport-023-220-247 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CNC=N1 SLZIZIJTGAYEKK-CIJSCKBQSA-N 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
230000035772 mutation Effects 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
230000006911 nucleation Effects 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
101150012154 nupG gene Proteins 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000000399 orthopedic effect Effects 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
RYZUEKXRBSXBRH-CTXORKPYSA-N pancreastatin Chemical compound C([C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(N)=O)C1=CN=CN1 RYZUEKXRBSXBRH-CTXORKPYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
229920000515 polycarbonate Polymers 0.000 description 1
239000004417 polycarbonate Substances 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
229920002635 polyurethane Polymers 0.000 description 1
239000004814 polyurethane Substances 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
230000004481 post-translational protein modification Effects 0.000 description 1
230000002980 postoperative effect Effects 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
239000012521 purified sample Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000010076 replication Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
101150098466 rpsL gene Proteins 0.000 description 1
229960002101 secretin Drugs 0.000 description 1
OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 description 1
238000005204 segregation Methods 0.000 description 1
108010052031 septide Proteins 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
230000035483 skin reaction Effects 0.000 description 1
231100000430 skin reaction Toxicity 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
238000000527 sonication Methods 0.000 description 1
230000005236 sound signal Effects 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
SRYYCRXKYKWXDQ-PTGKCMAJSA-N success Chemical compound O([C@H]1CCC[C@@H](OC(=O)C[C@H]2[C@@H]3C=C[C@@H]4C[C@H](C[C@H]4[C@@H]3C=C2C(=O)[C@@H]1C)O[C@H]1[C@@H]([C@H](OC)[C@@H](OC)[C@H](C)C1)OC)CC)[C@H]1CC[C@H](N(C)C)[C@@H](C)O1 SRYYCRXKYKWXDQ-PTGKCMAJSA-N 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000013589 supplement Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000012360 testing method Methods 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
229940034199 thyrotropin-releasing hormone Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
238000013271 transdermal drug delivery Methods 0.000 description 1
238000011282 treatment Methods 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
239000012137 tryptone Substances 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
230000000007 visual effect Effects 0.000 description 1
239000012138 yeast extract Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/635—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/815—Protease inhibitors from leeches, e.g. hirudin, eglin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Endocrinology (AREA)
Veterinary Medicine (AREA)
Gastroenterology & Hepatology (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Analytical Chemistry (AREA)
Epidemiology (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Radiology & Medical Imaging (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Toxicology (AREA)
Zoology (AREA)
Pharmacology & Pharmacy (AREA)
Tropical Medicine & Parasitology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CA002220060A 1995-06-06 1996-06-06 A method for increasing the electrotransport flux of polypeptides Abandoned CA2220060A1 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/468,275		1995-06-06
US08/468,275 US5747453A (en)	1995-06-06	1995-06-06	Method for increasing the electrotransport flux of polypeptides

Publications (1)

Publication Number	Publication Date
CA2220060A1 true CA2220060A1 (en)	1996-12-12

Family

ID=23859150

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002220060A Abandoned CA2220060A1 (en)	1995-06-06	1996-06-06	A method for increasing the electrotransport flux of polypeptides

Country Status (13)

Country	Link
US (2)	US5747453A (it)
JP (1)	JPH11507634A (it)
AU (1)	AU6264296A (it)
BE (1)	BE1009752A5 (it)
BR (1)	BR9609148A (it)
CA (1)	CA2220060A1 (it)
DE (1)	DE19681438B4 (it)
FR (1)	FR2735133B1 (it)
GB (1)	GB2316083B (it)
IE (1)	IE960414A1 (it)
IT (1)	IT1285404B1 (it)
NL (1)	NL1003284C2 (it)
WO (1)	WO1996039423A2 (it)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6333189B1 (en)	1996-06-06	2001-12-25	Alza Corporation	Method of making an electrotransport device
EP0922467A3 (en) *	1997-12-12	2000-05-24	Takeda Chemical Industries, Ltd.	Iontophoretic drug delivery
US8480580B2 (en)	1998-04-30	2013-07-09	Abbott Diabetes Care Inc.	Analyte monitoring device and methods of use
US8465425B2 (en)	1998-04-30	2013-06-18	Abbott Diabetes Care Inc.	Analyte monitoring device and methods of use
US6949816B2 (en) *	2003-04-21	2005-09-27	Motorola, Inc.	Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US9066695B2 (en)	1998-04-30	2015-06-30	Abbott Diabetes Care Inc.	Analyte monitoring device and methods of use
US8688188B2 (en)	1998-04-30	2014-04-01	Abbott Diabetes Care Inc.	Analyte monitoring device and methods of use
US8346337B2 (en)	1998-04-30	2013-01-01	Abbott Diabetes Care Inc.	Analyte monitoring device and methods of use
US6175752B1 (en)	1998-04-30	2001-01-16	Therasense, Inc.	Analyte monitoring device and methods of use
US8974386B2 (en)	1998-04-30	2015-03-10	Abbott Diabetes Care Inc.	Analyte monitoring device and methods of use
US6560471B1 (en)	2001-01-02	2003-05-06	Therasense, Inc.	Analyte monitoring device and methods of use
DE60331226D1 (de)	2002-05-24	2010-03-25	Medtronic Inc	Verfahren und dna-konstrukte zur produktion von polypeptiden mit hoher ausbeute
EP1554302A4 (en) *	2002-05-24	2006-05-03	Restoragen Inc	DNA RECOMBINATION METHODS AND PRODUCTS FOR HIGH-YIELD PRODUCTION OF POLYPEPTIDES
WO2003099854A2 (en) *	2002-05-24	2003-12-04	Nps Allelix Corp.	Method for enzymatic production of glp-2(1-33) and glp-2-(1-34) peptides
ME01366B (me) *	2003-11-21	2013-12-20	Nps Allelix Corp	POSTUPAK ZA PROIZVODNJU PEPTIDA 2 NALIK NA GLUKAGON l NJIHOVIH ANALOGA
WO2006045503A1 (en)	2004-10-19	2006-05-04	Lonza Ag	Method for solid phase peptide synthesis
ES2551305T3 (es) *	2005-12-28	2015-11-17	Alza Corporation	Formulaciones terapéuticas estables

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4250878A (en) *	1978-11-22	1981-02-17	Motion Control, Inc.	Non-invasive chemical species delivery apparatus and method
US4382529A (en) *	1980-12-15	1983-05-10	Drdlik Frank J	Sanitary dispensing closure
CA1231306A (en) *	1983-03-03	1988-01-12	Erich Hochuli	Purification of interferon
US4631211A (en) *	1985-03-25	1986-12-23	Scripps Clinic & Research Foundation	Means for sequential solid phase organic synthesis and methods using the same
US4722726A (en) *	1986-02-12	1988-02-02	Key Pharmaceuticals, Inc.	Method and apparatus for iontophoretic drug delivery
DE3703321A1 (de) *	1986-09-01	1988-03-10	Transcutan Gmbh	Therapievorrichtung zur anwendung von elektrischem strom
AU609769B2 (en) *	1987-02-10	1991-05-09	Drug Delivery Systems Inc.	Electrolytic transdermal delivery of proteins
US5080646A (en) *	1988-10-03	1992-01-14	Alza Corporation	Membrane for electrotransport transdermal drug delivery
CA2057035A1 (en) *	1989-07-10	1991-01-11	Sherwood R. Lehrman	Somatotropin analogs
US5516512A (en) *	1989-08-14	1996-05-14	Gist-Brocades, N.V.	N- and C-terminal truncation and deletion mutants of human interleukin-3
US5240913A (en) *	1989-08-18	1993-08-31	Biogen, Inc.	Inhibitors of thrombin
EP0429842B1 (en) *	1989-10-27	1996-08-28	Korea Research Institute Of Chemical Technology	Device for the transdermal administration of protein or peptide drug
NZ237202A (en) *	1990-02-23	1994-01-26	Bristol Myers Squibb Co	Composition containing beta-lactam antibiotic and cationic oligopeptide
USH1160H (en) *	1990-11-26	1993-04-06		Iontophoretic delivery of peptides
DK10191D0 (da) *	1991-01-22	1991-01-22	Novo Nordisk As	Hidtil ukendte peptider
US5270170A (en) *	1991-10-16	1993-12-14	Affymax Technologies N.V.	Peptide library and screening method
CA2087087C (en) *	1992-01-22	2000-07-18	Burton H. Sage, Jr.	Molecules for iontophoretic delivery
US5312326A (en) *	1992-06-02	1994-05-17	Alza Corporation	Iontophoretic drug delivery apparatus
US5814603A (en) *	1992-06-12	1998-09-29	Affymax Technologies N.V.	Compounds with PTH activity
WO1993025197A1 (en) *	1992-06-12	1993-12-23	Affymax Technologies N.V.	Compositions and methods for enhanced drug delivery
EP0646128A1 (en) *	1992-06-15	1995-04-05	Scios Inc.	Glucagon-like peptide and insulinotropin derivatives
ATE211655T1 (de) *	1993-09-22	2002-01-15	Hisamitsu Pharmaceutical Co	Iontophoresematrix
US5387189A (en) *	1993-12-02	1995-02-07	Alza Corporation	Electrotransport delivery device and method of making same
DE4404168A1 (de) *	1994-02-10	1995-08-17	Hoechst Ag	Hirudinderivate und Verfahren zu deren Herstellung

1995
- 1995-06-06 US US08/468,275 patent/US5747453A/en not_active Expired - Lifetime
1996
- 1996-06-05 IE IE960414A patent/IE960414A1/en not_active IP Right Cessation
- 1996-06-05 IT IT96TO000495A patent/IT1285404B1/it active IP Right Grant
- 1996-06-06 BR BR9609148A patent/BR9609148A/pt not_active Application Discontinuation
- 1996-06-06 AU AU62642/96A patent/AU6264296A/en not_active Abandoned
- 1996-06-06 DE DE19681438T patent/DE19681438B4/de not_active Expired - Fee Related
- 1996-06-06 WO PCT/US1996/009647 patent/WO1996039423A2/en active Application Filing
- 1996-06-06 FR FR9607003A patent/FR2735133B1/fr not_active Expired - Fee Related
- 1996-06-06 JP JP9501922A patent/JPH11507634A/ja active Pending
- 1996-06-06 NL NL1003284A patent/NL1003284C2/nl not_active IP Right Cessation
- 1996-06-06 CA CA002220060A patent/CA2220060A1/en not_active Abandoned
- 1996-06-06 GB GB9725980A patent/GB2316083B/en not_active Expired - Fee Related
- 1996-06-06 BE BE9600518A patent/BE1009752A5/fr not_active IP Right Cessation
1998
- 1998-01-15 US US09/007,466 patent/US6313092B1/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
IT1285404B1 (it)	1998-06-03
US5747453A (en)	1998-05-05
DE19681438B4 (de)	2010-02-04
ITTO960495A1 (it)	1997-12-05
WO1996039423A2 (en)	1996-12-12
ITTO960495A0 (it)	1996-06-05
GB9725980D0 (en)	1998-02-04
GB2316083A (en)	1998-02-18
US6313092B1 (en)	2001-11-06
WO1996039423A3 (en)	1997-01-30
DE19681438T1 (de)	1998-07-23
JPH11507634A (ja)	1999-07-06
BR9609148A (pt)	1999-02-23
FR2735133B1 (fr)	1998-02-13
GB2316083B (en)	2000-01-19
AU6264296A (en)	1996-12-24
NL1003284C2 (nl)	1997-03-20
FR2735133A1 (fr)	1996-12-13
IE960414A1 (en)	1996-12-11
BE1009752A5 (fr)	1997-07-01
NL1003284A1 (nl)	1996-12-09

Legal Events

Date	Code	Title	Description
2003-05-23	EEER	Examination request
2011-06-06	FZDE	Discontinued

Publication	Publication Date	Title
US5747453A (en)	1998-05-05	Method for increasing the electrotransport flux of polypeptides
US6333189B1 (en)	2001-12-25	Method of making an electrotransport device
JP2709817B2 (ja)	1998-02-04	抗凝固ペプチド
US5521283A (en)	1996-05-28	Anti-obesity proteins
US5559208A (en)	1996-09-24	Anti-obesity proteins
DE69719798T2 (de)	2004-02-12	Periphäre verabreichung von glp-1 analogen und derivate zur reguleirung der fettleibigkeit
US5552524A (en)	1996-09-03	Anti-obesity proteins
US5532336A (en)	1996-07-02	Anti-obesity proteins
EP0730661A1 (en)	1996-09-11	Compounds with pth activity and recombinant dna vectors encoding same
CA2252458A1 (en)	1997-10-30	Conjugates of lipophilic moieties and fragments of vasoactive intestinal peptide (vip)
AU2004298424A1 (en)	2005-06-30	Novel GLP-1 compounds
US20090275877A1 (en)	2009-11-05	Method of Enhancing Electrotransport Polypeptide Flux By Amino Acid Substitution with Histidine
JP2008542364A (ja)	2008-11-27	副甲状腺ホルモン、緩衝液、および安定剤を含んでなる安定化された副甲状腺ホルモン組成物
US5563245A (en)	1996-10-08	Anti-obesity proteins
CN1034577C (zh)	1997-04-16	制备具有血管舒缓激肽拮抗作用的肽类的方法
US5204328A (en)	1993-04-20	Peptides having atrial natriuretic factor activity
WO1988003537A1 (en)	1988-05-19	Novel peptides
EP0246795A2 (en)	1987-11-25	Synthetic natriuretic peptides
JPH09504423A (ja)	1997-05-06	修飾マキサディランタンパク質、その調製と使用、および該タンパク質をコードするｄｎａ
JPH04501259A (ja)	1992-03-05	Ｃｒｆ拮抗体
JP2003514532A (ja)	2003-04-22	生成物の産生量を最適化するための核酸構築体
AU1938599A (en)	1999-07-12	Beta-lipotropin and uses thereof
JPH04234327A (ja)	1992-08-24	血小板凝集阻害活性を有するヒルディンの類似体
CA2040649A1 (en)	1991-10-25	Growth hormone releasing factor analogs
MXPA00006123A (en)	2001-07-03	Beta-lipotropin and uses thereof